My long-term career goal is to develop an ethical framework to guide both clinicians and policy-makers regarding the genetic screening and testing of behavioral and developmental disorders. Because of my training in Internal Medicine, Pediatrics, Developmental Disabilities, and Medical Ethics, I am uniquely qualified to pursue this goal and to become an independent investigator in this field. The career development plans outlined in this K23 application will enhance the training and experience I have had to date and will provide additional guidance and focus to hone my skills. The genetic diagnosis of behavioral and developmental disorders is ethically complex because 1) these are life-span disorders with variable age of symptom onset; 2) they challenge the traditional Mendelian paradigm in which a single genotype correlates with a single disease phenotype; and 3) the diagnosis or its possibility often carry significant social stigma for the individual and the family. Proposed screening programs for Fragile X Syndrome (FXS), the most common cause of inherited mental retardation (MR), highlight the significant ethical challenges of diagnosing a condition when the meaning of a genotype varies across the lifespan. The FMR-1 gene is pleiotropic, causing more than one clinically-unrelated condition. Full mutations in the gene lead to FXS with child-onset MR and serious behavioral problems. Premutations cause premature ovarian failure and Fragile X Tremor Ataxia Syndrome in adults. Existing data about FMR-1 diagnostic strategies have largely ignored the complexities of pleiotropy. Therefore, there is no current consensus about who should be tested, what information should be disclosed to patients before testing and after a positive result, and the nature of a carriers' obligation to disclose their diagnosis to family members. In order to inform arguments for and against proposed screening programs and diagnostic testing guidelines, I will perform a comprehensive assessment about the risks and benefits of FMR-1 carrier diagnosis. Using qualitative and quantitative methodologies, I will examine the attitudes of primary stakeholders towards Fragile X newborn screening and FMR-1 carrier detection across the lifespan, and how the diverse meanings of the diagnosis influence decisions about familial disclosure. The results of the proposed research will be used to develop an R01 application examining the lifetime risks and benefits of carrying a genetic diagnosis for these conditions. [unreadable] [unreadable] [unreadable]